1. FIELD OF THE INVENTION
This invention relates to a controlled absorption pharmaceutical formulation and, in particular, to a controlled absorption methyldopa formulation.
2. DESCRIPTION OF THE PRIOR ART
Methyldopa (3-hydroxy-.alpha.-methyl-L-tyrosine) is an antihypertensive agent which it has been suggested may act centrally by stimulating alpha-adrenergic receptors. It inhibits the decarboxylation of dopa to dopamine and consequently reduces the amount of noradrenaline formed from dopamine. When administered orally the effects of methyldopa may appear after about 2 hours and reach a maximum in 6 to 8 hours, although the maximum hypotensive effect may not occur until the second day of treatment; some effect is still usually apparent 24 hours after a dose. Methyldopa is used in the treatment of moderate to severe hypertension. It acts by reducing the standing blood pressure and also reduces the supine blood pressure.
The usual initial dose by mouth is the equivalent of 250 mg of anhydrous methyldopa twice or thrice daily for two days; this is then adjusted by small increments or decrements not more frequently than every other day according to the response of the patient. The usual maintenance dosage is the equivalent of 0.5 to 2 g of anhydrous methyldopa daily.
A thiazide diuretic is frequently administered simultaneously with methyldopa to combat oedema which is sometimes observed with methyldopa therapy.
Only about one half of an oral dose of methyldopa is absorbed, and peak plasma concentrations occur after about 3 to 6 hours. In persons with normal renal function, 80 or 90% of the drug has been reported to be eliminated from the body in 48 hours. Of the methyldopa eliminated in the urine, about 25% is unchanged and the remainder is as metabolites, mainly a mono-O-sulphate of methyldopa.
It is an object of the present invention to provide a controlled absorption form of methyldopa which is suitable for once daily administration, which is characterised by a high degree of absorption, which is largely invariable from patient to patient, and by significant blood levels of methyldopa which are maintained for an extended period after administration.